Lipoprotein(a) and Long-Term Cardiovascular Risk in a Multi-Ethnic Pooled Prospective Cohort

This pooled prospective cohort study combined data from 27,756 participants across major US multi-ethnic cardiovascular epidemiology studies to examine the long-term (20+ year) relationship between Lp(a) concentration and ASCVD outcomes in a primary prevention population, stratified by race/ethnicity, sex, and diabetes status.

Lp(a) at the ≥90th percentile versus <50th percentile was associated with an HR of 1.46 for composite ASCVD events. Significant risk elevation began at the 75th percentile (HR 1.18). The strongest individual endpoint associations were for MI (HR 1.66) and coronary revascularization (HR 1.68). Critically, there was no interaction by sex or race/ethnicity — the Lp(a) risk association was consistent across Black, Hispanic, White, and Chinese-American participants, and in men and women equally. However, there was a significant interaction with diabetes (p=0.0056): among diabetic patients at the ≥90th percentile of Lp(a), the HR for ASCVD was 1.92 versus 1.41 without diabetes.

The consistency of Lp(a)‘s predictive association across race/ethnicity is important because Lp(a) concentrations differ substantially by ancestry: Black individuals have approximately 2-fold higher Lp(a) than White individuals, and the threshold for clinical action (≥50 mg/dL or ≥125 nmol/L) may need to be re-examined in the context of race-specific reference ranges. This study’s consistent HR across races suggests that the relative risk increase per unit Lp(a) is similar regardless of ancestry — the absolute risk implications differ because baseline Lp(a) levels and cardiovascular risk differ.

The diabetes-Lp(a) interaction — nearly 2-fold ASCVD risk at elevated Lp(a) with diabetes — identifies diabetic patients as a priority population for Lp(a) screening and future Lp(a)-lowering interventions.

We rate the evidence strong. A large multi-ethnic pooled cohort study in 27,756 primary prevention participants demonstrating consistent Lp(a)-ASCVD risk associations across races and sexes, with amplified risk in diabetic patients — one of the most comprehensive modern datasets supporting universal Lp(a) screening as a primary prevention tool.